The objectives of this proposal are (1) to study and to compare experimental renal cell cancer (E-RCa) with human renal cell cancer (H- RCa) and (2) to search for better methods for the diagnosis and evaluation and treatment of H-RCa. Methods and concepts developed over the last 3 years in the study of E-RCa will be expanded and applied to H-RCa. Clinical and laboratory evidence links renal carcinoma and the sex steroids in both tumorigenesis and treatment. In the male hamster kidney, which develops E-RCa during administration of estrogens, we have detected a specific and significant amount of estrogen binding to a macromolecule in the cytosol and have shown its absence in other non- target tissue of the hamster or rat. This binding may represent an important step in renal tumorigenesis and the macromolecule should be further characterized and investigated in H-RCa. Steroid receptors will be assayed by methods currently used in our laboratory and synthesis of specific tumor proteins will be elucidated by double-isotope labelling experiments. In vitro sensitivity of H-RCa steroid receptor to steroids and other drugs may suggest an assay for the selection of a drug in the treatment in individual patients. Enzyme abnormalities have been found in the blood of patients with renal cell cancer and we have found them in E-RCa; isoenzyme determinations (of phosphatases, transaminases, dehydrogenases, and decarboxylases) will be made in neoplastic, other abnormal and normal renal tissue and serum and urine before, during and after treatment. Diagnostically useful isoenzyme patterns of H-RCa may emerge, making it possible to correlate certain patterns with prognosis or responsiveness to therapeutic modalities, the importance of this is obvious. Alternatively, specific neoplasms may show unique patterns and these may be useful in patient follow up studies or evaluation of further treatment modalities. Certain H-RCa isoenzyme patterns may resemble E-RCa patterns and thus form the basis for further study, along lines perhaps, of examining human tumorigenesis as described above. Additionally, if E-RCa isoenzyme patterns resemble H-RCa patterns the animal model may be used in an as yet undeveloped drug surveillance protocol.